Acute myeloid leukemia (hereafter also referred to as “AML”) is a hematological malignancy with a poor prognosis that often occurs in adults, and the 5-year survival rate thereof is predicted to be 20%. At present, it is possible to temporarily reduce the number of AML cells to a level below the detection limit through AML treatment. This condition is referred to as “complete remission.” However, AML often recurs after achieving complete remission, and for many patients, recurrent AML results in death. Accordingly, there is an urgent need to prevent recurrence and establish a radical treatment method for AML.
While conventional chemotherapeutic agents would realize temporary remission of AML, its recurrence has been an issue of concern. In particular, a very low survival rate in cases of recurrence has been a serious issue of concern.
To date, the present inventors have demonstrated that elimination of leukemia stem cells (hereafter also referred to as “LSCs”) is critical for achieving radical cure for AML and that the LSCs are generally in the stationary phase of a cell cycle in bone marrow niches (Patent Document 1 and Non-Patent Documents 4 and 5). They have also demonstrated LSC-specific genes on the basis of gene expression comparison between LSCs and normal hematopoietic stem cells (hereafter also referred to as “HSCs”) (Patent Document 2 and Non-Patent Document 6).
Patent Document 3 describes that 5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidin-4-amine, which is represented by a general formula encompassing numerous compounds, would inhibit various types of kinase functions and is effective for treatment of various types of diseases, including leukemia.
Also, Patent Document 4 describes 5,7-disubstituted-7H-pyrazolo[3,4-d]pyrimidin-4-amine having kinase inhibitory activity.
However, neither Patent Document 3 nor Patent Document 4 provide any concrete evidence that supports the kinase inhibitory activity or pharmacological activity of any compounds.